We found that the binding of 125I-low-density lipoprotein to fetal liver low-density lipoprotein receptor rose progressively with the increase in fetal age. During this period, total cholesterol and low-density lipoprotein-cholesterol levels in fetal serum declined significantly. The correlation coefficients between fetal age and concentration of serum total cholesterol and low-density lipoprotein cholesterol were -0.80 (p less than 0.001) and -0.77 (p less than 0.001), respectively. A significant inverse correlation also existed between the liver low-density lipoprotein receptor activity and the serum total cholesterol (r = -0.96, p less than 0.001) and low-density lipoprotein cholesterol (r = -0.95, p less than 0.001) but not high-density lipoprotein cholesterol. It is suggested that the low-density lipoprotein receptors in human fetal liver may play a key role in the regulation of the serum cholesterol levels during gestation.